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Role of Prostaglandin I2 in Airway Remodeling Induced by Repeated Allergen Challenge in Mice

Department of Pharmacology, Gifu Pharmaceutical University, Gifu; and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan

Address correspondence to: Hiroichi Nagai, Prof., Ph.D., Department of Pharmacology, Gifu Pharmaceutical University, 5–6-1 Mitahora-higashi, Gifu 502–8585, Japan. E-mail: nagai{at}gifu-pu.ac.ip

Recently, we demonstrated that prostaglandin (PG)I2 has a regulatory role in allergic responses through the receptor, IP; however, the role of PGI2 in airway remodeling associated with chronic airway inflammation has not been elucidated. In the present study, we examined the role of PGI2 in allergen-induced airway remodeling using IP gene–deficient mice. Mice were sensitized to ovalbumin (OVA) with alum, and exposed daily for 3 wk to aerosolized OVA. Twenty-four hours after the final antigen inhalation, bronchoalveolar lavage, biochemical, and histopathologic examinations were performed. In wild-type mice, prolonged allergen exposure in sensitized animals induced the increases in the numbers of inflammatory leukocytes (including eosinophils and lymphocytes), levels of T helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13), levels of OVA-specific immunoglobulin (Ig)E and IgG1 in serum, and amount of hydroxyproline in the right lungs associated with transforming growth factor-ß1 levels in bronchoalveolar lavage fluid. Moreover, goblet cell hyperplasia and subepithelial fibrosis were also appreciated after repeated allergen challenge. In contrast, the disruption of IP gene significantly augmented all these parameters. These findings suggest that PGI2 has a regulatory role in allergen-induced airway remodeling as well as airway eosinophilic inflammation, Th2 cytokine production and IgE production, and that a PGI2 agonist is a therapeutic approach for the treatment of airway remodeling in allergic asthma.

Abbreviations: bronchoalveolar lavage fluid, BALF • bovine serum albumin, BSA • enzyme-linked immunosorbent assay, ELISA • interferon, IFN • immunoglobulin, Ig • interleukin, IL • ovalbumin, OVA • periodic acid-Schiff, PAS • prostaglandin, PG • transforming growth factor, TGF • T helper type 2, Th2

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